The Voice of Transplantation in the UK UK Guidelines on Pancreas and Islet Transplantation September 2019 Compiled by a Working Party of The British Transplantation Society NHS Evidence accredited provider NHS Evidence - provider by NICE www.evidence.nhs.uk British Transplantation Society Guidelines © British Transplantation Society www.bts.org.uk CONTENTS 1 Introduction...........................................................................................................4 1.1 The Need for Guidelines………………………………………………………..4 1.2 Process of Writing and Methodology………………………………….………5 1.3 Contributing Authors…................................................................................5 1.4 Declarations of Interest……………………………………………………...….7 1.5 Grading of Recommendations…………………………………………...…….8 1.6 Abbreviations…………………………...………………………………...……..9 1.7 Definitions and Scope……………………………………………………...….10 1.8 Disclaimer……………………………………………………………...……….11 2 Executive Summary of Recommendations......................................................13 3 Ethics...................................................................................................................20 3.1 Definitions..................................................................................................20 3.2 Pancreas Transplantation: Introduction.....................................................21 3.3 Pancreas Transplantation: The Donor Perspective...................................23 3.4 Pancreas Transplantation: The Recipient Perspective.............................23 3.5 Pancreas Transplantation: The Transplant Team Perspective.................24 3.6 Islet Transplantation..................................................................................24 3.7 BTS Ethics Committee..............................................................................25 4 Organ Availability and Allocation......................................................................26 4.1 Pancreas and Islet Allocation Policy in the United Kingdom.....................26 4.2 Pancreas and Islet Transplantation in the UK and the use of DCD Donors.......................................................................................................27 4.3 Rates and Causes of Organ Discard.........................................................28 5 Donor selection: Pancreas.................................................................................30 5.1 Introduction................................................................................................30 5.2 Deceased Donor Risk Factors..................................................................30 5.3 Deceased Donor Management.................................................................34 5.4 Deceased Donor Organ Retrieval.............................................................35 5.5 Organ Preservation and Perfusion Technologies......................................36 5.6 Organ Assessment at the Implanting Centre............................................37 6 Donor Selection: Islets.......................................................................................42 6.1 Deceased Donor Risk Characteristics and Risk Indices...........................42 6.2 Deceased Donor Management.................................................................43 6.3 Deceased Donor Organ Retrieval.............................................................43 6.4 Preservation for Islet Transplantation.......................................................44 6.5 Novel Preservation Technologies in Islet Transplantation........................44 6.6 Organ Quality Assessment at the Implanting Centre before Islet Isolation.....................................................................................................46 7 Recipient Selection: Pancreas...........................................................................50 7.1 Introduction................................................................................................51 7.2 Survival Benefits of Pancreas Transplantation..........................................51 7.3 Quality of Life and Co-morbidity Benefits of Pancreas Transplantation....52 7.4 Patient Assessment Prior to Pancreas Transplantation............................53 7.5 Discussing Transplant Options..................................................................60 2 8 Recipient Selection: Islets.................................................................................65 8.1 Introduction................................................................................................65 8.2 Benefits of Islet Transplantation................................................................66 8.3 Patient Assessment Prior to Islet Transplantation.....................................67 8.4 Discussing Transplant Options..................................................................70 9 Pancreas Transplantation and Peri-operative Care.........................................74 9.1 Introduction................................................................................................75 9.2 Workbench Preparation of the Pancreas...................................................75 9.3 Pancreas Implantation................................................................................81 9.4 Re-transplantation.....................................................................................84 9.5 Peri-operative Care...................................................................................85 10 Islet Isolation, Infusion, and Peri-operative Care.............................................97 10.1 Introduction................................................................................................97 10.2 Pancreas Retrieval....................................................................................97 10.3 Islet Isolation Procedure............................................................................97 10.4 Islet Transplantation................................................................................101 10.5 Peri-operative Care.................................................................................101 11 Histocompatibility and Immunosuppression.................................................107 11.1 Introduction..............................................................................................107 11.2 Donor HLA Typing……………….............................................................108 11.3 Recipient HLA Typing and Matching.......................................................109 11.4 Recipient Antibody Screening.................................................................110 11.5 Definition of Unacceptable Mismatches..................................................111 11.6 The Donor / Recipient Crossmatch Test.................................................112 11.7 Immunosuppression for Pancreas Transplantation.................................115 11.8 Immunosuppression for Islet Transplantation.........................................116 11.9 Development of HLA-specific Antibodies after Pancreas or Islet Transplantation........................................................................................117 12 Recipient Outcomes: Pancreas Transplantation...........................................124 12.1 Introduction..............................................................................................124 12.2 Standard Outcomes Measures after Pancreas Transplantation.............125 12.3 Challenges in Reporting Outcomes for Pancreas Transplantation.........129 13 Recipient Outcomes: Islet Transplantation....................................................136 13.1 Introduction..............................................................................................137 13.2 Standard Outcomes Measures after Islet Transplantation......................137 13.3 Immunological Monitoring in Islet Transplantation..................................144 14 Appendix: Summary Table of Outcome Measures in SPK Transplantation………..….149 3 1 INTRODUCTION 1.1 The Need for Guidelines These are the first guidelines on pancreas or islet transplantation published by the British Transplantation Society. Given the complexity of these treatments, the associated risks, and the multiple treatment options available to patients with insulin- dependent diabetes, this is perhaps surprising. It is hoped that these guidelines will inform clinical teams and patients regarding treatment options, provide guidance on clinical management, and suggest possible avenues for research and audit. Guidelines on islet transplantation have been produced alongside those on pancreas transplantation as the treatment modalities are, at present, complementary. In addition, the United Kingdom is unique in that the deceased donor islet and pancreas allocation schemes are combined. It therefore makes sense for these guidelines to cover both treatments, with the expectation that a joint approach to assessing the patient with insulin-dependent diabetes will enable closer working between islet and pancreas transplant teams and optimal patient outcomes. The authors and editors are aware that many recommendations within this document are for improved data returns. We hope that better data collection and an increased awareness of these issues will help provide much needed evidence for future iterations of this document. We encourage other national transplant organisations around the world to improve data gathering on pancreas and islet recipients, and to publish